Last updated: 2021-08-22

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Overview

We selected the results for pathways have >40 genes from the results regressing out <= 10 PEER factors

We added colocalization analysis for the pairs show sign consistency (at p-value < 0.002), the loci are +-250kb/500kb from the reported SNPs.

We just listed the pairs show sign consistency(at p-value < 0.002 from adaptive resampling) in the tables below.

‘pval_in_resampling_2’ in the tables means the p-value from adaptive resampling. ‘pval_in_resampling’ in the tables were computed from 1000 times resampling.

Enrichment summary – computed from ACAT p-values for all pairs

total pairs num_pval_acat < 0.05 enrichment num_pval_acat < 0.01 enrichment num_pval_acat < 0.001 enrichment
B cell 20540 6117 5.956183057 1399 6.811100292 170 8.27653359
CD14 21320 7675 7.199812383 1880 8.818011257 195 9.14634146
CD15 19110 4744 4.964939822 1486 7.77603349 206 10.7796965
T cell (CD4) 21450 5706 5.32027972 1095 5.104895105 89 4.14918415

Enrichment Summary – computed from resampling p-values for pairs have >=2 SNPs

1000 times resampling

adaptive resampling

Barplot to show the number of SNPs have FDR <0.2 that each pair contains

Detailed results for 6 cell types

B cell

ACAT summary

Warning in instance$preRenderHook(instance): It seems your data is too big
for client-side DataTables. You may consider server-side processing: https://
rstudio.github.io/DT/server.html

Example: top pathway from B-cell, EUR.IBD_pwy174_pc5, ACAT p = 1E-58, 2 SNPs at FDR < 0.2 (rs142770866 in chr19, rs9271176 in MHC). It is related to Antigen processing and presentation.

Other three pathways are also driven by these two SNPs: EUR.IBD_pwy182_pc5 – Hematopoietic cell lineage, EUR.IBD_pwy275_pc5 (another SNP rs35260072 on chr5 also drives this pathway) – Leishmaniasis and EUR.IBD_pwy331_pc4 – Viral myocarditis.

effectsize fitting summary

lymph_pwy270_pc1 - Shigellosis Shigella impairs T lymphocyte dynamics in vivo

lymph_pwy283_pc1 - Hepatitis C Hepatitis C virus infection of human T lymphocytes is mediated by CD5

lymph_pwy291_pc1 - Herpes simplex virus 1 infection Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection

mcv_pwy289_pc4 - Human T-cell leukemia virus 1 infection Provirus load was inversely correlated with hemoglobin (r = -0.11), mean corpuscular volume (r = -0.15)

mpv_pwy176_pc4 - Toll-like receptor signaling pathway In addition to their role in hemostasis, platelets participate in innate immunity and inflammation owing to the expression of toll-like receptors (TLR), which recognize inflammatory signals, triggering platelet functional responses

rbc_pwy314_pc3 - Breast cancer Red blood cells usually live for about 120 days but breast cancer and treatments may shorten that lifespan, causing anemia. With fewer red blood cells there to carry oxygen, your body may not function as well as it should. rbc_pwy314_pc3_rs551238 PP4 == 0.65

SNP details

Checking the reverse causality

**The suffix "_reverse" are the results for traits -> LV (using all candidate SNPs after LD Clumping), the suffix "_rremove" are the results for traits -> LV (using all candidate SNPs after LD Clumping but remove the SNPs have fdr < 0.2)**

Colocalization results

+-250kb from the SNP

+-500kb from the SNP

monocyte CD14

ACAT summary

Warning in instance$preRenderHook(instance): It seems your data is too big
for client-side DataTables. You may consider server-side processing: https://
rstudio.github.io/DT/server.html

effectsize fitting summary

EUR.IBD_pwy183_pc5 - Natural killer cell mediated cytotoxicity Additionally, NK cells can have a role in the pathogenesis of gut autoimmune inflammatory bowel diseases (IBDs)

baso_pwy287_pc1 - Influenza A Influenza A virus enhances basophil histamine release and the enhancement is abolished by carbohydrates

mchc_pwy284_pc5 - Hepatitis B Chronic hepatitis is associated with increased hemoglobin level in patients with end-stage renal disease mchc_pwy284_pc5_rs28687655 PP4 == 0.58, mchc_pwy284_pc5_rs4737010 pp4 ==0.57

neut_pwy236_pc1 - Cushing syndrome Blood cell counts showed that Cushing’s syndrome patients had significantly lower lymphocytes, but a higher total white blood cell count. They also had increased numbers of neutrophil cells.

SNP details

Checking the reverse causality

**The suffix "_reverse" are the results for traits -> LV (using all candidate SNPs after LD Clumping), the suffix "_rremove" are the results for traits -> LV (using all candidate SNPs after LD Clumping but remove the SNPs have fdr < 0.2)**

Colocalization results

+-250kb from the SNP

+-500kb from the SNP

neutrophils CD15

ACAT summary

effectsize fitting summary

pct_pwy142_pc2 - mTOR signaling pathway ROS Promote Ox-LDL-Induced Platelet Activation by Up-Regulating Autophagy Through the Inhibition of the PI3K/AKT/mTOR Pathway

SNP details

Checking the reverse causality

**The suffix "_reverse" are the results for traits -> LV (using all candidate SNPs after LD Clumping), the suffix "_rremove" are the results for traits -> LV (using all candidate SNPs after LD Clumping but remove the SNPs have fdr < 0.2)**

Colocalization results

+-250kb from the SNP

+-500kb from the SNP

T cell(CD4)

ACAT summary

Warning in instance$preRenderHook(instance): It seems your data is too big
for client-side DataTables. You may consider server-side processing: https://
rstudio.github.io/DT/server.html

effectsize fitting summary

EUR.CD_pwy124_pc1 - Phosphatidylinositol signaling system Phosphatidylinositol signaling system

EUR.CD_pwy300_pc1 - Colorectal cancer

lymph_pwy290_pc5 - Kaposi sarcoma-associated herpesvirus infection Primary B Lymphocytes Infected with Kaposi’s Sarcoma-Associated Herpesvirus Can Be Expanded In Vitro and Are Recognized by LANA-Specific CD4+ T Cells lymph_pwy290_pc5_rs2737275 PP4 == 0.54

plt_pwy115_pc3 - Calcium signaling pathway Agonist-induced elevation in cytosolic Ca2+ concentrations is essential for platelet activation in hemostasis and thrombosis. It occurs through Ca2+ release from intracellular stores and Ca2+ entry through the plasma membrane (PM).

SNP details

Checking the reverse causality

**The suffix "_reverse" are the results for traits -> LV (using all candidate SNPs after LD Clumping), the suffix "_rremove" are the results for traits -> LV (using all candidate SNPs after LD Clumping but remove the SNPs have fdr < 0.2)**

Colocalization results

+-250kb from the SNP

+-500kb from the SNP

T cell(CD8)

effectsize fitting summary

lymph_pwy143_pc4 - PI3K-Akt signaling pathway 1. Regulation of PI-3-kinase and Akt signaling in T lymphocytes and other cells by TNFR family molecules, 2. Role of PI3K/Akt signaling in memory CD8 T cell differentiation

rbc_pwy217_pc4 - Estrogen signaling pathway The results demonstrate that estrogen acts directly on the stem cells to increase their proliferation and the number of red blood cells they generate

SNP details

Checking the reverse causality

**The suffix "_reverse" are the results for traits -> LV (using all candidate SNPs after LD Clumping), the suffix "_rremove" are the results for traits -> LV (using all candidate SNPs after LD Clumping but remove the SNPs have fdr < 0.2)**

Colocalization results

+-250kb from the SNP

+-500kb from the SNP

platelet

effectsize fitting summary

SNP details

Checking the reverse causality

**The suffix "_reverse" are the results for traits -> LV (using all candidate SNPs after LD Clumping), the suffix "_rremove" are the results for traits -> LV (using all candidate SNPs after LD Clumping but remove the SNPs have fdr < 0.2)**

Colocalization results

+-250kb from the SNP

+-500kb from the SNP


sessionInfo()
R version 3.6.1 (2019-07-05)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Scientific Linux 7.4 (Nitrogen)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.2.19-el7-x86_64/lib/libopenblas_haswellp-r0.2.19.so

locale:
 [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
 [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
 [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
 [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
 [9] LC_ADDRESS=C               LC_TELEPHONE=C            
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] workflowr_1.6.2

loaded via a namespace (and not attached):
 [1] Rcpp_1.0.5        rstudioapi_0.11   whisker_0.3-2     knitr_1.30       
 [5] magrittr_1.5      R6_2.4.1          rlang_0.4.8       highr_0.8        
 [9] stringr_1.4.0     tools_3.6.1       DT_0.15           xfun_0.18        
[13] git2r_0.26.1      crosstalk_1.1.0.1 htmltools_0.5.0   ellipsis_0.3.1   
[17] rprojroot_1.3-2   yaml_2.2.1        digest_0.6.25     tibble_3.0.3     
[21] lifecycle_0.2.0   crayon_1.3.4      later_1.1.0.1     htmlwidgets_1.5.2
[25] vctrs_0.3.4       promises_1.1.1    fs_1.5.0          glue_1.4.2       
[29] evaluate_0.14     rmarkdown_1.13    stringi_1.5.3     compiler_3.6.1   
[33] pillar_1.4.6      backports_1.1.10  jsonlite_1.7.1    httpuv_1.5.1     
[37] pkgconfig_2.0.3